PROJECT SUMMARY Research Project: Blood pressure (BP) management after endovascular mechanical thrombectomy (EVT) for large vessel acute ischemic stroke (AIS) can critically influence brain reperfusion, and thereby patient outcomes. Current guidelines recommend allowing higher than normal BP in the 24 hrs after an EVT without strong evidence. Our preliminary results demonstrate that lower post-EVT systolic BP (SBP) associate with better outcomes. Although low SBP targets are assumed to compromise brain perfusion, no data exist to definitely demonstrate any relationship of harm with post-EVT SBP targets. Such safety assessment of lower SBP targets is a critical prerequisite to conduct larger studies to evaluate their efficacy in improving outcomes of EVT-treated patients. We will conduct the Blood Pressure after Endovascular Stroke Therapy-II (BEST-II) trial, where 120 AIS patients successfully treated with an EVT will be randomized to three SBP targets (180, <160, and <140 mmHg) to 1) assess the harm of lower SBP targets and 2) determine the probability (hypothesized to be 25%) of a positive phase III efficacy trial of lower SBP targets to improve patient outcomes. To assess the harm, we will test the null hypotheses that lower SBP targets do not worsen brain ischemia or 90-day functional outcome in patients beyond a level considered safe. This proposal will generate high quality data for the planning of a large, multicenter efficacy trial. Collectively, this set of trials will lead to evidence-based guideline generation for the optimal post-EVT BP management in AIS patients. Candidate: Working close with her mentors over the past two years, Dr. Eva Mistry designed, led, and successfully completed a large, prospective, multi-institutional study (BEST-I) to demonstrate the association of improved outcomes with lower SBP in EVT-treated AIS patients. This proposal is the direct result of this preliminary work. Her long-term goal is to be a leader in novel designs and electronic facilitation of acute stroke trials to ensure efficient testing of new stroke treatments and improve patient outcomes. Career Development: To achieve her long-term goal, Dr. Mistry will follow an integrated career development plan. Her rigorous training will include coursework, personalized mentoring from mentors and advisors, and experiential training to achieve mastery in 1) trial implementation in acute and critical care settings, 2) adaptive and platform trial designs, 3) electronic facilitation of clinical trials, and 4) leadership skills. Environment: Vanderbilt University Medical Center (VUMC) is the largest comprehensive stroke center in the middle Tennessee and performs over 100 EVTs annually. As a Clinical and Translational Science Awarded institution with a large pool of NIH-funded investigators and leaders in acute and critical care clinical trials, novel trial designs, biostatistics, and clinical informatics, VUMC provides an ideal environment with myriad opportunities and support resources for Dr. Mistry to successfully accomplish her research and career goals to become an independent investigator.